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Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice

Abstract

Aims/hypothesis

Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis.

Methods

Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms.

Results

The CBTs of adiponectin knockout mice (Adipoq −/−) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq −/− mice significantly blunted β adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq −/− mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing β3-adrenergic receptor expression in brown adipocytes.

Conclusions/interpretation

This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.

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Abbreviations

Acrp30:

Adipocyte complement-related protein of 30 kDa (adiponectin)

Ad-Acrp30:

Adenovirus-encoded adipocyte complement-related protein of 30 kDa (adiponectin)

Ad-GFP:

Adenovirus-encoded green fluorescent protein

AMPK:

AMP-activated protein kinase

ATGL:

Adipose triacylglycerol lipase

βAR:

β-adrenergic receptor

BAT:

Brown adipose tissue

CBT:

Core body temperature

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HSL:

Hormone-sensitive lipase

iBAT:

Interscapular brown adipose tissue

ISO:

Isoprenaline

Myf5:

Myogenic factor 5

PGC-1α:

Peroxisome proliferator–activated receptor γ co-activator 1 α

PKA:

Protein kinase A

RT:

Room temperature

SNS:

Sympathetic nervous system

UCP1:

Uncoupling protein 1

WAT:

White adipose tissue

WT:

Wild type

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Acknowledgements

We thank Y.-H. Tseng (Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA) and P. Scherer (The University of Texas Southwestern Medical Center, Dallas, TX, USA) for providing brown pre-adipocytes and Adipoq −/− mice, respectively.

Funding

This work was supported by grants DK080418 (JS), HD069634 (JS), DK095132 (JS) and R01DK075916 (GF) from the National Institutes of Health and 5-I01-BX000702 (N-WC) from the Department of Veterans Affairs.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

LQ, HY, CB and BL performed experiments, analysed data and revised the article. GF, N-WC and JSc contributed study design, reviewing and editing of this manuscript. JSh is responsible for the integrity of this work as a whole and conceived and supervised the study and wrote the manuscript. All authors approved the final version of this manuscript.

Author information

Correspondence to Jianhua Shao.

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Qiao, L., Yoo, H.s., Bosco, C. et al. Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice. Diabetologia 57, 1027–1036 (2014). https://doi.org/10.1007/s00125-014-3180-5

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Keywords

  • Adiponectin
  • Brown adipose tissue
  • Energy expenditure
  • Thermogenesis